Association between <scp>MTHFR C</scp>677<scp>T</scp> polymorphism and diabetic nephropathy in the <scp>C</scp>hinese population: An updated meta‐analysis and review

Xiong, Xuan; Lin, Xiaokun; Xiao, Xiao; Qin, Danping; Zhou, Dian-Yuan; Hu, Jiangsheng; Liu, Yan; Zhong, Xiaoshi

doi:10.1111/nep.12541

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…Metaanalysis of MTHFR polymorphisms revealed significant heterogeneity between studies for both 677C>T and 1298A>C. Further, there was no evidence for publication bias for these polymorphisms. In consistent with our results, a series of earlier published meta-analyses provided evidence of association between MTHFR 677C>T polymorphism and DN risk in various ethnicities (39)(40)(41)(42)(43)(44)(45). With regards to MTHFR 1298A>C only one meta-analysis performed in which no association between MTHFR 1298A>C and DN risk was observed (44).…”

Section: Sensitivity Analysis and Publication Biassupporting

confidence: 91%

Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms and the risk of diabetic nephropathy; a meta-analysis

Gupta

Sharma

Lakkakula³

et al. 2019

J Renal Inj Prev

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Methylenetetrahydrofolate reductase (MTHFR) is involved in the homocysteine metabolism. Two common variants of MTHFR gene (677C>T and 1298A>C), have been reported to reduce the MTHFR enzyme activity and leading to plasma hyperhomocysteinemia. There are a number of recent case-control studies that investigated the association between the MTHFR polymorphism and diabetic nephropathy (DN), albeit with inconsistent results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of MTHFR with susceptibility to DN. A literature search was conducted on PubMed, Embase and Google scholar from inception till March 18, 2019. For MTHFR 677C>T analysis, a total of 23 studies including DM controls (3095 cases and 3187 DM controls) and 12 studies including non-DM controls (1590 cases and 2052 nonDM controls) were taken. For MTHFR 1298A>C analysis, a total of 7 studies using DM controls (959 cases and 1209 DM controls) and 3 studies using non-DM controls (400 cases and 802 nonDM controls) were taken. Meta-analysis showed that mutant genotypes of the 677C>T (OR: 1.58; 95%CI: 1.16-2.14) and 1298A>C (OR: 1.38; 95%CI: 1.16-1.65) polymorphisms in the MTHFR gene were associated with increased risk of DN (diabetic kidney disease). MTHFR 677C>T and 1298A>C polymorphisms revealed significant heterogeneity between studies. Further, there was no evidence for publication bias for these polymorphisms. In conclusion, this meta-analysis provides strong evidence that MTHFR 677C>T and 1298A>C polymorphisms may be associated with increased risks of DN. However, further studies are still needed to accurately determine whether MTHFR genetic polymorphisms are associated with susceptibility to DN.

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Section: Sensitivity Analysis and Publication Biassupporting

confidence: 91%

Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms and the risk of diabetic nephropathy; a meta-analysis

Gupta

Sharma

Lakkakula³

et al. 2019

J Renal Inj Prev

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“…Methylenetetrahydrofolate reductase A1298C polymorphism and diabetes risk: evidence from a meta-analysis T2DM [77] Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta-analysis and review DN [78] Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to diabetic nephropathy in Chinese type 2 diabetic patients: a meta-analysis T2DM and DN [79] Increasing prevalence of gestational diabetes mellitus when carrying the T variant allele of the MTHFR gene C677T polymorphism: a systematic review and meta-analysis Gestational diabetes [80] Relationship between methylenetetrahydrofolate reductase (MTHFR) A1298C gene polymorphism and type 2 diabetic nephropathy risk: a meta-analysis T2DM and DN [81] A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy DR [82] Genetics of diabetic neuropathy: Systematic review, meta-analysis and trial sequential analysis DN [83] Methylenetetrahydrofolate reductase C677T polymorphism and type 2 diabetes mellitus in Chinese population: a meta-analysis of 29 case-control studies T2DM [84] Plausible relationship between homocysteine and obesity risk via MTHFR gene: a meta-analysis of 38,317 individuals implementing Mendelian randomization Obesity risk [85] Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach T2DM [86] Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis DN [87] ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis T2DM [88] Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus T2DM and DN [89] Association between MTHFR C677T polymorphism and diabetic nephropathy or diabetes mellitus risk: need for clarification of data in a recent meta-analysis T2DM and DN [90] Methylenetetrahydrofolate reductase C677T polymorphism and diabetic retinopathy risk: a meta-analysis of the Chinese population DR [91] The relationship between methylenetetrahydrofolate reductase C677T polymorphism and diabetic retinopathy: A meta-analysis in multi-ethnic groups DR [92] MTHFR gene C677T polymorphism and type 2 diabetic nephropathy in Asian populations: a meta-analysis DN [93] Genetic susceptibility to type 2 diabetes: a global meta-analysis studying the genetic differences in Tunisian populations T2DM [94] Genetic risk of type 2 diabetes in populations of the African continent: A systematic review and meta-analyses T2DM…”

Section: Study Title Associated Disease Referencementioning

confidence: 99%

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

2021

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The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the MTHFR gene, especially C677T, have been associated with various diseases, including cardiovascular diseases (CVDs), cancer, inflammatory conditions, diabetes, and vascular disorders. The C677T MTHFR polymorphism is thought to be the most common cause of elevated Hcy levels, which is considered an independent risk factor for CVD. This polymorphism results in an amino acid change from alanine to valine, which prevents optimal functioning of the enzyme at temperatures above 37 °C. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and increased risk for CVD. There is much evidence in favour of this association, while several studies have concluded that the polymorphism cannot be used to predict CVD development or progression. This review discusses current research regarding the C677T polymorphism and its relationship with CVD, inflammation, diabetes, and epigenetic regulation and compares the evidence provided for and against the association with CVD.

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“…These prior studies indicate significant associations between the MTHFR C677T polymorphism and an increased risk of various diseases and disorders, including lung cancer (67), non-syndromic cleft lip and palate (68), depression (69), diabetic nephropathy (70) in the North China population, but such associations were absent FIGURE 4 | Sensitivity analysis through the deletion of each study to reflect the individual influence on the calculated ORs in a heterozygous genetic model of MTHFR C677T polymorphism. (67,68) or weaker (69,70) in the South China population. One possible explanation for this may be related to people's different folate and vitamin B12 concentrations in the two regions.…”

Section: Discussionmentioning

confidence: 94%

Association Between MTHFR C677T Polymorphism and Susceptibility to Autism Spectrum Disorders: A Meta-Analysis in Chinese Han Population

Liu

Che

et al. 2021

Front. Pediatr.

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Prior studies have examined the influence of MTHFR C677T on autism susceptibility, however, there are no consensus conclusions and specific analyses of a Chinese population. This meta-analysis included a false-positive report probability (FPRP) test to comprehensively evaluate the association of MTHFR C677T polymorphism with autism susceptibility among a Chinese Han population. A large-scale literature retrieval was conducted using various databases including PubMed, Embase, Wan Fang, and the Chinese National Knowledge Infrastructure (CNKI) up to July 31, 2020, with a total of 2,258 cases and 2,073 controls included. The strength of correlation was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs). MTHFR C677T showed a significant correlation with increased ASD susceptibility under all genetic models (T vs. C, OR = 1.89, 95% CI 1.28 to 2.79; TT vs. CC: OR = 2.44, 95% CI 1.43 to 4.15; CT vs. CC, OR = 1.73; 95% CI 1.19 to 2.51; CT + TT vs. CC: OR = 2.03, 95% CI 1.31 to 3.15; TT vs. CT + CC, OR = 1.95, 95% CI 1.21 to 3.13). Stratification analysis by region also revealed a consistent association in the Northern Han subgroup, but not in the Southern Han subgroup. Pooled minor allele frequency (MAF) of 30 studies were 45% in Northern Han and 39% in Southern Han. To avoid a possible “false positive report,” we further investigated the significant associations observed in the present meta-analysis using the FPRP test, which consolidated the results. In conclusion, MTHFR C677T polymorphism is associated with the increased risk of autism in China, especially in Northern Han. For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism, especially in Northern Han populations. In the future, more well-designed studies with a larger sample size are expected.

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Association between MTHFR C677T polymorphism and diabetic nephropathy in the Chinese population: An updated meta‐analysis and review

Cited by 11 publications

References 22 publications

Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms and the risk of diabetic nephropathy; a meta-analysis

Association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C>T and 1298A>C polymorphisms and the risk of diabetic nephropathy; a meta-analysis

Methylenetetrahydrofolate (MTHFR), the One-Carbon Cycle, and Cardiovascular Risks

Association Between MTHFR C677T Polymorphism and Susceptibility to Autism Spectrum Disorders: A Meta-Analysis in Chinese Han Population

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